1. Field of the Invention
This invention relates to certain novel 2,6-dichlorophenyl substituted amino-imidazole derivatives and their non-toxic, pharmaceutically acceptable acid addition salts. This invention also relates to a process for preparing the derivatives and to a process for employing the derivatives and their salts as anti-hypertensive agents in mammals. This invention further relates to novel intermediates and their non-toxic, pharmaceutically acceptable acid salts and to a process of using such compounds as diuretic agents in mammals.
2. Summary of the Prior Art
It is known in the art that a number of imidazole compounds and their derivatives exhibit pharmacological properties. Thus, for example, U.S. Pat. No. 2,944,061 describes derivatives, such as 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole (i.e., metronidazole) or their acid addition salts, as exhibiting antiprotozoal activity.
A further type of imidazole derivative which may be used as an antagonist to H-2 type histamine receptors is disclosed in British Pat. No. 1,397,436. Compounds which exemplify this type of imidazole derivative include N-cyano-N'-methyl-N"-[2-[[(5-methyl-1H-imidazol-4-yl) methyl]thio]ethyl]guanidine (i.e., cimetidine).
Imidazoline derivatives having pharmacological properties are also known in the art. These derivatives are structurally different from the imidazole derivatives primarily by possessing only a single carbon to carbon covalent bond within the ring structure. Exemplary of the imidazoline derivatives are the vasoconstrictor and adrenergic agents 2-benzyl-2-imidazoline (i.e., tolazoline) and 2-(1-naphthylmethyl)imidazoline (i.e., naphazoline) as described in U.S. Pat. No. 2,161,938.
Another example of a pharmacologically active imidazoline derivative is set forth in U.S. Pat. No. 3,202,660. This patent describes 2-(2,6-dichloroanilino)-2-imidazoline (i.e., clonidine) as being an anti-hypertensive agent.
The preparation and anti-hypertensive activity of chlonidine and various phenyl substituted derivatives of clonidine is discussed in P.B.M.W.M. Timmermans et al, J. of the Royal Netherlands Chem. Soc., 96/2, Feb. 1978. Other clonidine related compounds which exhibit anti-hypertensive and anti-secretory activity are described in Jen et al, J. of Medicinal Chem., Volume 18, No. 1 (1975) and German Offenlegungsschuft No. 2,618,756.
It has been found that a number of the pharmacologically active imidazole and imidazoline derivatives possess serious drawbacks. Thus, for example, it is recognized that some of the known derivatives do not display anti-hypertensive activity or are relatively toxic which makes dosage regulation critical. Other derivatives exhibit undesirable side effects. Illustrative of the latter type of such derivatives is clonidine itself which causes a temporary rise in blood pressure at the beginning of administration.